The fundamental purpose of these studies is to define the mechanisms by which peptide growth factors stimulate replication in human fibroblasts and to determine if and how these processes are altered during aging. Human fibroblasts derived from donors of several ages will be examined for alterations in the quantity of somatomedin-C necessary for replication and changes in the responsiveness of this cell type to growth factors which are synergistic with somatomedin-C. The effect of aging on basal and hormone stimulated somatomedin production by fibroblasts will be studied. The effects of mitogens such as human growth hormone on somatomedin production will be determined. Experiments will be performed to test the hypothesis that somatomedin produced locally can stimulate the proliferation of adjacent fibroblasts. A model system for studying the biosynthesis of somatomedin will be developed. The effects of known hormonal stimuli on somatomedin synthesis will be quantitated. The physiochemical properties of the synthetic product will be determined. Post-proliferative fibroblasts will be compared to early passage fibroblasts derived from young and old donors; parameters such as sensitivity to somatomedin and production of somatomedin will be compared. The results of these investigations should establish whether age related changes in peptide growth factor requirements are determinants of cellular aging. The substantiation of the hypothesis that a growth factor secreted by fibroblasts can control the proliferation of adjacent cells will establish a new mechanism for the control of cellular proliferation. The delineation of the factors which control somatomedin production and their alteration during the normal aging process should provide a basis for future studies into aging disorders.